2024-03-28T23:19:28Zhttp://buleria.unileon.es/oai/requestoai:buleria.unileon.es:10612/151562022-11-04T13:01:22Zcom_10612_17col_10612_18
00925njm 22002777a 4500
dc
Maeso Alonso, Laura
author
Alonso-Olivares, Hugo
author
Martínez-García, Nicole
author
López-Ferreras, Lorena
author
Villoch-Fernández, Javier
author
Puente-Santamaría, Laura
author
Colas-Algora, Natalia
author
Fernández-Corona, Alfonso
author
Lorenzo-Marcos, María Elena
author
Jiménez, Benilde
author
Holmgren, Lars
author
Wilhelm, Margareta
author
Millan, Jaime
author
del Peso, Luis
author
Claesson-Welsh, Lena
author
Marqués Martínez, Margarita
author
Marín Vieira, María Carmen
author
[EN] Preservation of blood vessel integrity, which is critical for normal physiology and organ function, is controlled at multiple levels, including endothelial junctions. However, the mechanism that controls the adequate assembly of endothelial cell junctions is not fully defined. Here, we uncover TAp73 transcription factor as a vascular architect that orchestrates transcriptional programs involved in cell junction establishment and developmental blood vessel morphogenesis and identify Angiomotin (AMOT) as a TAp73 direct transcriptional target. Knockdown of p73 in endothelial cells not only results in decreased Angiomotin expression and localization at intercellular junctions, but also affects its downstream function regarding Yes-associated protein (YAP) cytoplasmic sequestration upon cell–cell contact. Analysis of adherens junctional morphology after p73-knockdown in human endothelial cells revealed striking alterations, particularly a sharp increase in serrated junctions and actin bundles appearing as stress fibers, both features associated with enhanced barrier permeability. In turn, stabilization of Angiomotin levels rescued those junctional defects, confirming that TAp73 controls endothelial junction dynamics, at least in part, through the regulation of Angiomotin. The observed defects in monolayer integrity were linked to hyperpermeability and reduced transendothelial electric resistance. Moreover, p73-knockout retinas showed a defective sprout morphology coupled with hemorrhages, highlighting the physiological relevance of p73 regulation in the maintenance of vessel integrity in vivo. We propose a new model in which TAp73 acts as a vascular architect integrating transcriptional programs that will impinge with Angiomotin/YAP signaling to maintain junctional dynamics and integrity, while balancing endothelial cell rearrangements in angiogenic vessels.
Maeso-Alonso, L., Alonso-Olivares, H., Martínez-García, N. et al. p73 is required for vessel integrity controlling endothelial junctional dynamics through Angiomotin. Cell. Mol. Life Sci. 79, 535 (2022). https://doi.org/10.1007/s00018-022-04560-3
1420-682X
https://link.springer.com/article/10.1007/s00018-022-04560-3
http://hdl.handle.net/10612/15156
10.1007/s00018-022-04560-3
1420-9071
Biología
p73 is required for vessel integrity controlling endothelial junctional dynamics through Angiomotin